Calcium carbonate (CaCO3), which exhibits excellent biocompatibility and bioactivity, is a well-established bone filling material for bone defects. Here, we synthesized CaCO3microspheres (CMs) to use as an intelligent carrier to load bone morphogenetic protein-2 (BMP-2). Subsequently, drug-loaded CMs and catalase (CAT) were added to methacrylated gelatin (GelMA) hydrogels to prepare a composite hydrogel for differential release of the drugs. CAT inside hydrogels was released with a fast rate to eliminate H2O2and generate oxygen. Constant BMP-2 release from CMs induced rapid osteogenesis. Resultsin vitroindicated that the composite hydrogels efficiently reduced the level of intracellular reactive oxygen species, preventing cells from being injured by oxidative stress, promoting cell survival and proliferation, and enhancing osteogenesis. Furthermore, animal experiments demonstrated that the composite hydrogels were able to inhibit the inflammatory response, regulate macrophage polarization, and facilitate the healing of bone defects. These findings indicate that a multi-pronged strategy is greatly expected to promote the bone healing by modulating pathological microenvironments.
Keywords: bone morphogenetic protein-2; bone regeneration; calcium carbonate; catalase; pH response; reactive oxygen species.
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